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Applications of Causally Defined Direct and

Indirect Effects in Mediation Analysis


using SEM in Mplus

Bengt Muthén

October 28, 2011


I thank Tihomir Asparouhov, Michael Sobel, Hendricks Brown, David MacKinnon, and
Judea Pearl for helpful advice

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Abstract

This paper summarizes some of the literature on causal effects in

mediation analysis. It presents causally-defined direct and indirect effects

for continuous, binary, ordinal, nominal, and count variables. The

expansion to non-continuous mediators and outcomes offers a broader

array of causal mediation analyses than previously considered in structural

equation modeling practice. A new result is the ability to handle mediation

by a nominal variable. Examples with a binary outcome and a binary,

ordinal or nominal mediator are given using Mplus to compute the effects.

The causal effects require strong assumptions even in randomized designs,

especially sequential ignorability, which is presumably often violated to

some extent due to mediator-outcome confounding. To study the effects

of violating this assumption, it is shown how a sensitivity analysis can

be carried out. This can be used both in planning a new study and in

evaluating the results of an existing study.

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1 Introduction
This paper considers mediation analysis (see, e.g., Baron & Kenny, 1986;

MacKinnon, 2008) as carried out in structural equation modeling (SEM;

see, e.g., Goldberger & Duncan, 1973; Jöreskog and Sörbom, 1979; Bollen,

1989). Mediation analysis in SEM uses the terms direct and indirect effects.

The implication that the direct and indirect effects produced by SEM are

causal effects has been criticized in e.g. Holland (1988) and Sobel (2008),

while generally interpreted with causal implications by others, e.g. Pearl

(2010, 2011a). The challenge in using mediation for causal inference comes

in interpreting the relationship between changes in the mediator and its

impact on the outcome, which cannot rely on inferential support from an

underlying randomized trial. SEM practitioners are left with a somewhat

confusing picture of what is accomplished with mediational analysis. To

exacerbate the problem, the causal inference literature is often difficult

to understand for researchers using SEM. Also, key researchers disagree

about the best language to use as seen in the recent debate in the journal

NeuroImage (Lindquist & Sobel, 2010, 2011; Glymour, 2011; Pearl, 2011b).

As a modest attempt to help clarify part of the picture, this paper

gives a summary of some of the key issues, showing relationships between

SEM effect concepts and causal effect concepts in mediation analysis, and

focusing on applications of mediation analyses with causally-defined direct

and indirect effects produced by Mplus. The paper shows that causally-

defined direct and indirect effects are not necessarily the same as effects

typically presented by SEM practitioners, and in several cases provide new

effects that have not been used in SEM practice. The causally-defined

effects can be obtained via extended types of SEM analyses. To claim that

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effects are causal, however, it is not sufficient to simply use the causally-

defined effects. A set of assumptions needs to be fulfilled for the effects to

be causal and the plausibility of these assumptions needs to be considered.

The paper presents causally-defined direct and indirect effects for

continuous, binary, ordinal, nominal, and count variables. The expansion

to non-continuous mediators and outcomes offers a broader array of causal

mediation analyses than previously considered in SEM practice. A new

result is the ability to handle mediation by a nominal variable. Examples

with a binary outcome and a binary, ordinal and nominal mediators are

given. The assumptions behind causal effects in mediation modeling

are discussed and sensitivity analyses of the possible distorting effects of

violations of the assumptions are exemplified. Extensions to moderated

mediation and latent variable mediation are discussed. For the paper to be

self-contained, an appendix gives derivations of the effects, most of which

can be found in the literature. Estimation is performed by maximum-

likelihood, weighted least-squares, and Bayesian analysis. The analyses can

be carried out by the free demo version of Mplus at www.statmodel.com.

An appendix gives the Mplus input scripts for all analyses.

2 A mediation model with treatment-

mediator interaction
Consider Figure 1 which corresponds to a randomized trial with a binary

treatment dummy variable x (0=control, 1=treatment), a covariate c, a

continuous mediator m, and a continuous outcome y, a situation examined

in detail by MacKinnon (2008). A special feature is that the treatment and

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mediator interact in their influence on the outcome y. This possibility is

important to the so-called MacArthur approach to mediation (Kraemer et

al., 2008). As pointed out in e.g. VanderWeele and Vansteelandt (2009), the

possibility of this interaction was emphasized in Judd and Kenny (1981) but

not in the influential Baron and Kenny (1986) article on mediation, and is

therefore often not explored. The interaction possibility is, however, stated

in James and Brett (1984) and more recently in Preacher et al. (2007). The

covariate c is useful in randomized studies to increase the power to detect

a treatment effect. Adding an interaction between c and x, a treatment-

baseline interaction effect on y can be explored; this type of moderated

mediation is discussed in Section 11.1. The model of Figure 1 is used to

first discuss the SEM concepts of direct and indirect effects and then the

corresponding causal concepts.

[Figure 1 about here.]

3 SEM concepts of direct and indirect

effects
Assuming linear relationships, Figure 1 translates into

yi = β0 + β1 mi + β2 xi + β3 xi mi + β4 ci + 1i , (1)

mi = γ0 + γ1 xi + γ2 ci + 2i , (2)

where the residuals 1 and 2 are assumed normally distributed with zero

means, variances σ12 , σ22 , and uncorrelated with each other and with the

predictors in their equations. SEM considers the reduced form of this model,

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obtained by inserting (2) in (1),

yi = β0 + β1 (γ0 + γ1 xi + γ2 ci + 2i ) + β2 xi + β3 xi (γ0 + γ1 xi + γ2 ci + 2i )+

β4 ci + 1i , (3)

= β0 + β1 γ0 + β1 γ1 xi + β3 γ0 xi + β3 γ1 x2i + β2 xi + β1 γ2 ci + β3 γ2 xi ci +

β4 ci + β1 2i + β3 xi 2i + 1i . (4)

First, assume no treatment-mediator interaction, that is, β3 = 0. In this

case, the reduced-form expression of (4) states that the direct effect of x on

y is β2 and the indirect effect via m is β1 γ1 . In both cases, the presence of

the covariate c implies that these statements are conditional on c. These

are the standard formulas used in mediation modeling.

Second, let β3 6= 0. In this case, the definitions of the direct and indirect

effect are perhaps less clear. One may consider the direct effect to be

β3 γ0 + β2 + β3 γ2 c, where the first term is included because γ0 is not

part of the influence of x on m and the third term is included for the same

reason. In this way, there can be a direct effect even if β2 = 0. One may

consider the indirect effect to be a sum composed of a main part β1 γ1 and

an interaction part β3 γ1 . In this way, there can be a indirect effect even if

β1 = 0.

It should be noted that the Mplus MODEL INDIRECT computations

are not valid for a model such as Figure 1 due to the treatment-mediator

interaction, but reports the direct effect as β2 and the indirect effect as

β1 γ1 . As shown in Section 5 the correct effects can, however, be computed

via MODEL CONSTRAINT.

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4 Causal inference concepts of direct and

indirect effects
Causally-defined direct and indirect effects were introduced in Robins and

Greenland (1992) and further elaborated in Pearl (2001) and Robins (2003).

Drawing on this work, some of the more accessible treatments of direct and

indirect causal effects are given in VanderWeele and Vansteelandt (2009),

see also Valeri and VanderWeele (2011), and Imai et al. (2010a,b). Valeri

and VanderWeele (2011) describe macros for SAS and SPSS, and Imai et

al. (2010c) describe the R program mediation.

The assumptions behind the causally-defined effects are important and

may often not be fulfilled in practice. VanderWeele and Vansteelandt (2009)

and Imai et al. (2010b) give formal, technical statements of the assumptions

using potential outcomes notation and provide proofs of identifiability.

Valeri and VanderWeele (2011) use simple language to summarize these

assumptions and their summary is quoted here:

”(i) no unmeasured confounding of the treatment-outcome rela-

tionship.

(ii) no unmeasured confounding of the mediator-outcome rela-

tionship.

(iii) no unmeasured treatment-mediator confounding

(iv) no mediator-outcome confounder affected by treatment”

Assumptions (i) and (iii) are fulfilled when X is a randomized treatment.

Assumptions (i) and (ii) are sufficient for the controlled direct effect defined

below. The direct and indirect effects defined below require all four

assumptions (although see Pearl, 2011c, footnote 5 for exceptions). This

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means that even with randomized treatment, direct and indirect effects

require that assumptions (ii) and (iv) be fulfilled. Taken together, this is

often referred to as the sequential ignorability assumption. Because the

mediator values are not randomized within treatment groups, assumptions

(ii) and (iv) may often not be fulfilled. As pointed out in VanderWeele and

Vansteelandt (2009), assumptions (i)-(iii) ”could potentially be satisfied,

at least approximately, by collecting data on more and more confounding

variables”. Assumption (iv), however, ”will be violated irrespective of

whether data is available for all such variables.” Even in randomized studies

this means that the causally-defined effects are biased unless assumptions

(ii) and (iv) hold, and if assumption (iv) does not hold causal effects cannot

be identified. Imai (2010a, b) and VanderWeele (2010) propose sensitivity

analyses to study the impact of violations of assumptions. A sensitivity

analysis is illustrated in a later section for both simulated and real data.

A key concept in the causal effect literature is a counterfactual or

potential outcome. Let Yi (x) denote the potential outcome that would have

been observed for that subject had the treatment variable X been set at the

value x, where x is 0 or 1 in the example considered here (in the following,

upper-case letters denote variables and lower-case letters values of these

variables). The Yi (x) outcome may not be the outcome that is observed for

the subject and is therefore possibly counterfactual. The effect of treatment

for a subject can be seen as Yi (1) − Yi (0), but is clearly not identified given

that a subject only experiences one of the two treatments. The average

effect E[Y (1) − Y (0)] is, however, identifiable if X is assigned randomly as

is the case in a randomized controlled trial. Similarly, let Y(x, m) denote

the potential outcome that would have been observed if the treatment for

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the subject was x and the value of the mediator M was m.

Following are definitions of the total, direct, and indirect effects. The

formulas are general, that is, not based on a particular model such as the

linear model for continuous variables of (1) and (2). Because of this, they

can be generalized to other types of variables.

The controlled direct effect is defined as

CDE(m) = E[Y (1, m) − Y (0, m) | C = c]. (5)

where M = m for a fixed value m. The first index of the first term is 1

corresponding to the treatment group and the first index of the second term

is 0 corresponding to the control group.

The direct effect (often called the pure or natural direct effect) does not

hold the mediator constant, but instead allows the mediator to vary over

subjects in the way it would vary if the subjects were given the control

condition. The direct effect is expressed as

DE = E[Y (1, M (0)) − Y (0, M (0)) | C = c] = (6)


Z ∞
= {E[Y | C = c, X = 1, M = m] − E[Y | C = c, X = 0, M = m]}
−∞

× f (M | C = c, X = 0) ∂M, (7)

where f is the density of M. A simple way to view this is to note that in

(6) Y’s first argument, that is x, changes values, but the second does not,

implying that Y is influenced by X only directly. The expression should be

read as the conditional expectation, given the covariate, of the difference

between the outcome in the treatment and control group when the mediator

is held constant at the values it would obtain for the control group. The

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right-hand side of (7) is part of what is referred to as the Mediation Formula

in Pearl (2009, 2011c).

The total indirect effect is defined as (Robins, 2003)

T IE = E[Y (1, M (1)) − Y (1, M (0)) | C = c] = (8)


Z ∞
= E[Y | C = c, X = 1, M = m] × f (M | C = c, X = 1) ∂M
−∞
Z ∞
− E[Y | C = c, X = 1, M = m] × f (M | C = c, X = 0) ∂M. (9)
−∞

A simple way to view this is to note that the first argument of Y in (8)

does not change, but the second does, implying that Y is influenced by X

due to its influence on M. The expression should be read as the conditional

expectation, given the covariate, of the difference between the outcome in

the treatment group when the mediator changes from values it would obtain

in the treatment group to the values it would obtain in the control group.

The name total indirect effect is used in Robins (2003), while Pearl (2001)

and VanderWeele and Vansteelandt (2009) call it the natural indirect effect.

The total effect is (Robins, 2003)

T E = E[Y (1) − Y (0) | C = c] (10)

= E[Y (1, M (1)) − Y (0, M (0)) | C = c]. (11)

A simple way to view this is to note that both indices are 1 in the first term

and 0 in the second term. In other words, the treatment effect on Y comes

both directly and indirectly due to M. The total effect is the sum of the

direct effect and the total indirect effect (Robins, 2003),

T E = DE + T IE. (12)

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The pure indirect effect (Robins, 2003) is defined as

P IE = E[Y (0, M (1)) − Y (0, M (0)) | C = c] (13)

Here, the effect of X on Y is only indirect via M. This is called the natural

indirect effect in Pearl (2001) and VanderWeele and Vansteelandt (2009).

The difference between TIE and PIE is shown below for the model of (1)

and (2).

4.1 Applying the causal effects to the mediation

model

The appendix Section 13.1 (see also the Appendix of VanderWeele &

Vansteelandt, 2009) shows how the direct effect in (7) and the total indirect

effect in (9), conditional on the value c, are explicated in terms of the

parameters of the model of (1) and (2) by integrating over the distribution

of M. The direct effect is

DE = β2 + β3 γ0 + β3 γ2 c. (14)

This agrees with the direct effect conjectured for the reduced form of the

SEM approach above, but the results are obtained via a clear definition.

The total indirect effect is

T IE = β1 γ1 + β3 γ1 . (15)

This agrees with the indirect effect conjectured for the reduced form of

the SEM approach above. The pure indirect effect excludes the interaction

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part,

P IE = β1 γ1 . (16)

In summary, the SEM estimates for the mediation model of Figure 1

can be used to express the causal direct and indirect effects. The causal

inference using potential outcomes clarifies how to conceptualize these

effects. As will be seen in the next sections, there is not necessarily a similar

agreement between effects used in SEM practice and the causal effect results

when either the outcome Y or the mediator M is not continuous. In fact,

the causally-defined effects to be presented have not been available in SEM

software until now.

5 Monte Carlo simulation of continu-

ous mediator, continuous outcome with

treatment-mediator interaction
Monte Carlo simulations are useful for planning purposes to determine the

sample size needed to recover parameter values well and to have sufficient

power to detect various effects. Mplus has quite general Monte Carlo

capabilities as is demonstrated in this paper; see also Muthén and Muthén

(1998-2010, chapter 12). For an application of a Monte Carlo study, see

Muthén and Muthén (2002).

Consider again the model of Figure 1 as explicated in (1) and (2), but

simplified to not include a covariate c. Note that the interaction between

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the treatment and the mediator in

yi = β0 + β1 mi + β2 xi + β3 xi mi + 1i (17)

can be expressed via a random slope β1i ,

yi = β0 + β1i mi + β2 xi + 1i (18)

β1i = β1 + β3 xi + i , (19)

where the residual  has not only zero mean but also zero variance. A

non-zero variance can also be handled and represents heteroscedasticity in

line with random coefficient regression shown in ex 3.9 in the Mplus User’s

Guide (Muthén & Muthén, 1998-2010). A non-zero variance is not pursued

here, however. Inserting (19) in (18) gives the same as (17).

This random slope approach to create an interaction is used in the Mplus

input for a Monte Carlo simulation shown in Section 14.1. 500 samples

of size 400 are generated in a first step. A second step analyzes the 400

samples in a model where an interaction term x × m is created and included

in the analysis model. MODEL CONSTRAINT is used to specify the causal

direct and indirect effects defined in Section 4. The effects are computed

by specifying NEW parameters derived from labeled model parameters.

Standard errors are automatically produced using the delta method. The

results are shown in Table 1 for the second step. The results for the first step

are exactly the same, except for a slight difference in the standard errors

using the MLR estimator instead of ML. The Mplus input gives comments

to describe the quantities derived from the model parameters. The new

parameters tie, pie, and de correspond to the indirect and direct effects

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of (15), (16), and (14). It is seen that all parameters are well recovered

and standard errors are well estimated. The last two columns show good

95% coverage and good power to reject that the parameter is zero. For

a description of how to interpret the Mplus Monte Carlo output, see pp.

362-365 of the User’s Guide, Muthén and Muthén (1998-2010). The setup

can be used for planning purposes to study coverage and power at different

sample sizes and effect sizes.

[Table 1 about here.]

Because the effects involve products of parameters, the distribution

of the effect estimates may not be well approximated by a normal

distribution. This is particularly the case with small sample sizes and in

situations with a binary mediator and/or a binary outcome. To account

for this non-normality of the effect distribution, ML estimation can use

bootstrapped standard errors and bootstrap-based confidence intervals.

The modification of the Mplus input is to request BOOTSTRAP=1000,

say, in the ANALYSIS command, and add CINTERVAL(BOOTSTRAP)

in the OUTPUT COMMAND. As an alternative, Bayesian analysis can

be used, where the parameter distributions do not have to be normal.

The Bayesian analysis produces posterior distributions and confidence

(credibility) intervals of the effects. This is accomplished simply by

specifying ESTIMATOR=BAYES in the ANALYSIS command.

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6 Mediation modeling with a binary out-

come and a continuous mediator


Consider next the case of Figure 1 where the outcome y is binary. This

replaces (1) with a corresponding probit or logistic regression equation.

In this case, the Mplus direct and indirect effects of SEM are defined

for a continuous latent response variable underlying the binary outcome

and therefore use the same formulas as before. This is also the approach

proposed in MacKinnon et al. (2007), considering a model without the

treatment-mediator interaction. The corresponding effects defined for the

observed binary outcome may be less well known, but have been presented

in Iamai et al. (2010a), and are restated here.

Considering a model with the treatment-mediator interaction, Vander-

Weele and Vansteelandt (2010) define causal effects for the observed binary

outcome. They consider logistic regression for (1) and assume that y

corresponds to a rare outcome. In this case, the indirect effect can be

expressed as an odds ratio that is approximately equal to

eβ1 γ1 +β3 γ1 , (20)

that is, using the same formula as in (15), but with parameters on the logit

scale.

This paper considers probit regression for y in (1) without an assumption

of the binary outcome being rare. Appendix Section 13.2 derives causally-

defined direct and indirect effects (see also Imai et al., 2010a, Appendix F).

Using the definition in (9), the causal total indirect effect is expressed as

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the probability difference

Φ[probit(1, 1)] − Φ[probit(1, 0)], (21)

using the standard normal distribution function Φ, and where for x, x’ =

0, 1 corresponding to the control and treatment group,

probit(x, x0 ) = [β0 +β2 x+β4 c+(β1 +β3 x)(γ0 +γ1 x0 +γ2 c)]/ v(x), (22)
p

where the variance v(x) for x = 0, 1 is

v(x) = (β1 + β3 x)2 σ22 + 1. (23)

where σ22 is the residual variance for the continuous mediator m. Although

not expressed in simple functions of model parameters, the quantity of (21)

can be computed and corresponds to the change in the y=1 probability

due to the indirect effect of the treatment (conditionally on c when that

covariate is present).

The total indirect effect odds ratio for the binary y related to the binary

x can be expressed as

Φ[probit(1, 1)]/(1 − Φ[probit(1, 1)])


. (24)
Φ[probit(1, 0)]/(1 − Φ[probit(1, 0)])

For any given data set, this odds ratio can be compared to that in (20)

computed via logistic regression and assuming that the outcome y is rare.

Using the definition in (13), the pure indirect effect is expressed as the

probability difference

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Φ[probit(0, 1)] − Φ[probit(0, 0)]. (25)

Using the definition in (6), the direct effect is expressed as the

probability difference

Φ[probit(1, 0)] − Φ[probit(0, 0)]. (26)

6.1 A closer look at the effects in a simple special

case

To put the causal indirect and direct effects in perspective, consider the

special case of no treatment-mediator interaction (β3 = 0) and no covariate

c. In this case the causal indirect effect Φ[probit(1, 1)] − Φ[probit(1, 0)] has

probit arguments

q
probit(1, 1) = [β0 + β2 + β1 γ0 + β1 γ1 ]/ β12 σ22 + 1, (27)
q
probit(1, 0) = [β0 + β2 + β1 γ0 ]/ β12 σ22 + 1. (28)

This may be compared to a naive approach of expressing the indirect effect

for the probit as the product β1 γ1 and considering the probability difference

Φ(a) − Φ(b) with and without this indirect effect, where

q
a = [β0 + β1 γ0 + β1 γ1 ]/ β12 σ22 + 1, (29)
q
b = [β0 + β1 γ0 ]/ β12 σ22 + 1. (30)

The difference between the causal and naive indirect effect approaches is

that the direct effect slope β2 plays a role in the former, but not in the

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latter.

Noting that Φ(b) = Φ[probit(0, 0)], the causal direct effect Φ[probit(1, 0)]−

Φ[probit(0, 0)] has probit arguments

q
probit(1, 0) = [β0 + β2 + β1 γ0 ]/ β12 σ22 + 1, (31)
q
probit(0, 0) = [β0 + β1 γ0 ]/ β12 σ22 + 1. (32)

A naive approach may instead focus on the direct effect β2 and consider

Φ(a0 ) − Φ(b0 ), where

q
a0 = [β0 + β2 ]/ β12 σ22 + 1, (33)
q
0
b = [β0 ]/ β12 σ22 + 1. (34)

This leaves out the β1 γ0 term of the causal approach.

The difference between the causal effects and the effects obtained by

what is called the naive approach has been studied in Imai et al. (2010a)

and Pearl (2011c). Imai et al. (2010a, Appendix E, p. 23) conducted

a Monte Carlo simulation study to show the biases, while Pearl (2011c)

presented graphs showing the differences.

In summary, the causal approach gives clear definitions of indirect and

direct effects. Alternative, naive, approaches do not have the same causal

interpretation.

6.2 Mplus computations

The direct and indirect effects can be estimated in Mplus using maximum-

likelihood. Standard errors of the direct and indirect causal effects are

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obtained by the delta method using the Mplus MODEL CONSTRAINT

command. Bootstrapped standard errors and confidence intervals are

also available, taking into account possible non-normality of the effect

distributions. Furthermore, Bayesian analysis is available in order to

describe the posterior distributions of the effects. Examples of Mplus

analysis are shown below.

It should be noted that changing from probit to logistic regression, not

assuming a rare outcome, does not lead to as simple expressions as in

(21) and (26). This is because in the logistic case the integration over

the mediator does not lead to an explicit form, but calls for numerical

integration.

Maximum-likelihood estimation using logistic regression is also available

in Mplus, where effects can be derived using approximate odds ratios under

the assumption of a rare outcome.

6.3 Distributional assumption for the mediator:

Latent response variable mediation

The direct and indirect effect formulas given above in the probit case assume

normality for the residual 2 in the mediator regression. This may be a

strong assumption and when it is violated the effects will be biased.

One type of non-normality may arise when the mediator can be viewed

as an ordered categorical (ordinal) variable. In this case, the approach of

Muthén (1984) may be taken where instead of the observed mediator, an

underlying continuous latent response variable is viewed as the relevant

mediator. In line with an ordered probit model, the observed mediator

categories are determined by the latent mediator variable falling below or

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exceeding thresholds as illustrated in Figure 2. Although the observed

ordinal mediator m has a non-symmetric distribution with the highest

frequency for m = 0, the latent mediator m∗ can still be normal conditional

on the covariates.

Figure 2 corresponds to the measurement relationship





 0 if m∗i ≤ τ1

mi =
 1 if τ1 < m∗i < τ2


if τ2 ≤ m∗i

 2

where for a latent response variable y ∗ behind the binary outcome y

yi∗ = β0 + β1 m∗i + β2 xi + β3 xi m∗i + β4 ci + 1i , (35)

m∗i = γ1 xi + γ2 ci + 2i . (36)

The key point is that the continuous latent response variable m∗ is used

not only as a dependent variable in (36) but also replaces the observed

m as a predictor in (35). This implies that the probit-based direct and

indirect causal effects of the previous section with a continuous mediator

are still valid. This type of model can be estimated in Mplus using weighted

least-squares and Bayesian analysis. An application is shown in Section 6.6.

[Figure 2 about here.]

6.4 Monte Carlo simulation with a binary out-

come and a continuous mediator

To study the behavior of maximum-likelihood and Bayesian estimation with

a binary outcome, a Monte Carlo study is carried out for a model like the

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one in Figure 1, using n = 200. The same two steps are used as in the Monte

Carlo study of Section 5. Data are generated using probit for the binary

outcome. Appendix Section 14.2 shows the Mplus input for Step 1 and the

Step 2 input for maximum-likelihood (the Bayes analysis simply changes to

ESTIMATOR=BAYES, deleting LINK=PROBIT). Causal effects in terms

of probabilities and odds ratios are expressed in MODEL CONSTRAINT

using the formulas presented in the beginning of this section.

Table 2 and Table 3 show the results for the two estimators (the Bayes

analysis uses FBITER=10000). It is seen that for both estimators all

parameters, including the causal effects, are well estimated with good

coverage.

[Table 2 about here.]

[Table 3 about here.]

Appendix Section 14.2 also shows the Mplus input for a Bayesian

analysis of the data generated in the first replication of the simulation. This

analysis produces the posterior distributions of all the parameters. Figure 3

shows the posterior for the odds ratio corresponding to the direct effect

(orde) and Figure 4 shows the posterior for the odds ratio corresponding

to the total indirect effect (ortie). It is seen that neither posterior is

close to normally distributed. Vertical lines at the tails show the upper

and lower limits of the Bayesian 95% credibility interval. Bayes has the

advantage that this interval is not symmetrically placed around the mean

as is the case when using the maximum-likelihood approach. In other

words, as seen in the Monte Carlo simulation, maximum-likelihood and

Bayes will give similar point estimates for these odds ratios but different

confidence/credibility intervals.

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[Figure 3 about here.]

[Figure 4 about here.]

6.5 Example 1: Aggressive behavior and juvenile

court record

Data for this example are from a randomized field experiment in Baltimore

public schools where a classroom-based intervention was aimed at reducing

aggressive-disruptive behavior among elementary school students. Figure 5

shows the Fall baseline aggression score as agg1, observed before the

intervention started. The variable agg1 is used as a covariate in the analysis

to strengthen the power to detect treatment effects. The mediator variable

agg5 is the aggression score in Grade 5 after the intervention ended. The

outcome juvcrt is a binary variable indicating whether or not the student

obtained a juvenile court record by age 18 or an adult criminal record. The

analysis to be presented involves n = 250 boys in treatment and control

classrooms with complete data. A further description of the data and

related analyses is given in Muthén et al. (2002).

The juvcrt outcome is not rare, but is observed for 50% of the sample.

The mediator agg5 is not normally distributed, but is quite skewed

with a heavy concentration at low values. The normality assumption of

Section 6, however, pertains to the mediator residual 2 and because the

covariate agg1 has a distribution similar to the mediator agg5, the agg5

distribution is to some extent driven by the agg1 distribution so that the

normality assumption for the residual may be a reasonable approximation.

Causal effect estimates are computed using the probit approach. They

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are compared with those of the logistic regression approach, mistakenly

assuming that the outcome juvcrt is rare.

[Figure 5 about here.]

Appendix Section 14.3 shows the Mplus input for maximum-likelihood

analysis of this model using probit and logit. The probit output is shown

in Table 4. It is seen that the treatment-mediator interaction (xm) is

not significant. The section New/additional parameters show the effect

estimates. The causal direct effect (direct) of (26) is not significant.

The causal indirect effect (indirect) of (21) is estimated as −0.064 and

is significant. This is the drop in the probability of a juvenile court record

due to the indirect effect of treatment. The odds ratio for the indirect

effect of (24) is estimated as 0.773 which is significantly different from one

(z = (0.773 − 1)/0.092 = −2.467). These findings can be compared with

the indirect and direct effects labeled ind and dir at the top of the new

parameters section, which use the regular definitions in (15) and (14), that

is, considering the continuous latent response variable for the outcome as

the relevant dependent variable.

[Table 4 about here.]

Using logistic regression instead, the maximum-likelihood estimate of

the odds ratio under the rare outcome assumption of (20) is 0.734 and

is also significantly different from one; see Table 5. This means that in

the current example, the probit and logistic approaches give quite similar

results despite the outcome not being rare.

[Table 5 about here.]

23
The Mplus input in Appendix Section 14.3 can be easily adapted to

other applications. The statements in the MODEL CONSTRAINT section

need not be changed if the same parameter labels are used in the MODEL

command. If there is no treatment-mediator interaction in the model, the

statement beta3 = 0 can be added in MODEL CONSTRAINT below the

NEW statement. Likewise, with no covariate c for the probit analysis,

beta4 = 0 is added. Note that in the probit analysis beta4 is multiplied by

zero, that is, the effect is evaluated at the average of the covariate c.

6.6 Example 2: Intentions to stop smoking

MacKinnon et al. (2007) analyzed the model shown in Figure 6. There

is no evidence of treatment-mediator interaction. The data are from a

drug intervention program for students in Grade 6 and 7 in Kansas City.

Schools were randomly assigned to treatment or control. The multilevel

aspect of the data is ignored here as in MacKinnon et al. (2007). The

mediator is the intention to use cigarettes in the following 2-month period,

measured about six months after baseline. The outcome is cigarette use in

the previous month, measured at follow-up. Cigarette use is observed for

18% of the sample. The data for n = 864 students are shown in Table 6.

[Figure 6 about here.]

[Table 6 about here.]

Table 6 shows that the intention mediator is not close to normally

distributed in either the treatment or control group. This means that the

normality assumption for the 2 residual is violated. Because of this, the

data are analyzed not only using the observed mediator approach but also

24
the latent response variable mediator approach discussed in Section 6.3.

In the former case, normality is (mistakenly) assumed for the continuous

mediator given the treatment dummy variable and maximum-likelihood

estimation is used. In the latter case normality is assumed for the

latent response variable given the treatment dummy variable, treating the

observed mediator as ordered categorical, and using weighted least-squares

estimation. Appendix Section 14.4 shows the Mplus inputs. Table 7 and

Table 8 show the results using probit for the observed and latent mediator

approach, respectively.

For the observed mediator approach using probit, the causal direct effect

odds ratio is 0.731, while the causal indirect odds ratio is 0.853. Using

logistic regression (not shown), the causal indirect odds ratio is 0.843, that

is, only slightly lower than the value for probit.

[Table 7 about here.]

[Table 8 about here.]

For the latent mediator approach using probit, the causal direct effect

odds ratio is 0.829, while the causal indirect odds ratio is 0.796. This means

that the latent mediator approach results in a stronger indirect effect and

a weaker direct effect relative to the observed mediator approach. A latent

mediator approach using logistic regression is not yet available in Mplus.

25
7 Mediation modeling with a binary me-

diator
When the mediator is binary, a latent mediator approach or an observed

mediator approach may be used. Taking a latent mediator approach leads

to the causal effect techniques described in the previous section. Taking

an observed mediator approach, the causal direct and indirect approach

described in Section 4 is still valid but needs to be explicated. The observed

binary mediator case is interesting because SEM-based direct and indirect

effects have not been developed in SEM software. Direct and indirect

effects for this case have, however, been discussed in Winship and Mare

(1983), although not from a causal inference perspective. Causal direct and

indirect effects for the case of a binary observed mediator and a continuous

outcome have been explicated in Valeri and VanderWeele (2011). This

section instead focuses on the case of a binary observed mediator and

a binary outcome. In VanderWeele and Vansteelandt (2009) and Valeri

and VanderWeele (2011) this is studied only in the special case of logistic

regression with a rare outcome. The general formulas of Section 4 can be

applied without a rare outcome assumption. Pearl (2010, 2011a) explicates

the effects in a general non-parametric way, without a need for probit or

logistic regression, although acknowledging that in practice such parametric

approaches are typically called for. The formulas are expressed here in terms

of both probit and logistic regression.

26
7.1 Causal effects with a binary mediator and a

binary outcome

In Section 4 the direct, total indirect, and pure indirect effects are defined

as

DE = E[Y (1, M (0)) − Y (0, M (0)) | C], (37)

T IE = E[Y (1, M (1)) − Y (1, M (0)) | C], (38)

P IE = E[Y (0, M (1)) − Y (0, M (0)) | C]. (39)

Appendix Section 13.3 shows that with a binary mediator and a binary

outcome these formulas lead to the expressions

DE = [FY (1, 0) − FY (0, 0)] [1 − FM (0)] + [FY (1, 1) − FY (0, 1)] FM (0),

(40)

T IE = [FY (1, 1) − Fy (1, 0)] [FM (1) − Fm (0)], (41)

P IE = [FY (0, 1) − Fy (0, 0)] [FM (1) − Fm (0)]. (42)

where FY (x, m) denotes P (Y = 1 | X = x, M = m) and FM (x) denotes

P (M = 1 | X = x), where F denotes either the standard normal or

the logistic distribution function corresponding to using probit or logistic

regression. These formulas agree with those of Pearl (2010, 2011a). The

following sections give two examples, applying these causal effects using

Mplus.

27
7.2 Pearl’s hypothetical binary case

Pearl (2010, 2011a) provided a hypothetical example with a binary

treatment X, a binary mediator M corresponding to the enzyme level in

the subject’s blood stream, and a binary outcome Y corresponding to being

cured or not. This example was also discussed on SEMNET in September

2011 (see web reference below). Table 9 shows the design of the example.

[Table 9 about here.]

The top part of the table suggests that the percentage cured is higher in

the treatment group for both enzyme levels and that the effect of treatment

is higher at enzyme level 1 than enzyme level 0. There is therefore a

treatment-mediator interaction in line with Figure 1, except with a binary

mediator and a binary outcome. Because of the non-linear expressions of

Section 7.1, however, the interaction should not be expected to take a simple

linear form as in Section 4.1. An analysis is needed to clarify what role the

enzyme mediator plays. While this can be done using the population values

of Table 9, a Monte Carlo simulation study is carried out to also study the

sampling behavior of the effects.

7.2.1 Monte Carlo simulation

Using a sample of n = 400, where the subjects have equal probability of

being in the control and treatment groups, Mplus Monte Carlo simulations

are carried out using the specifications of Table 9. Data are generated and

analyzed using both logit and probit. The Mplus inputs are shown in the

appendix Section 14.5, also giving the definitions of the quantities derived

from the model parameters. These include ratios of direct and indirect

28
effects relative to the total effect as in Pearl (2010, 2011a). The effects

are labeled de for direct effect, tie for total indirect effect (natural indirect

effect), pie for pure indirect effect, te for total effect, with ratios dete, tiete,

and piete. Furthermore, compdete refers to the direct effect complement

1 − de/te. Note that 1 − de/te = tie/te because te − de = tie, that is

te = de + tie.

The results for logit with maximum-likelihood estimation are shown in

Table 10, the results for probit with maximum-likelihood estimation are

shown in Table 11, and the results for probit with Bayesian estimation are

shown in Table 12. It is seen that all causal effects are well recovered, giving

good approximations to the values shown in Pearl (2010, 2011a).

The tables show a somewhat unusual situation where the y on m

regression slope would be insignificant at this sample size, but the xm

interaction regression slope would be significant. In terms of causal effects,

the interaction effect shows up most clearly in the difference between the

total indirect effect (tie) and the pure indirect effect (pie). Pearl (2011a)

focuses the interpretation on the direct effect complement (compdete =

1 − de/te which is the same as tiete = tie/te) and the pure indirect effect

ratio to total effect (piete = pie/te), concluding (the values referred to are

given in the Population column):

”We conclude that 30.4% of all recoveries is owed to the

capacity of the treatment to enhance the secretion of the enzyme,

while only 7% of recoveries would be sustained by enzyme

enhancement alone.”

Further discussion of this example by Pearl is available at

http://www.mii.ucla.edu/causality/wp-content/uploads/2011/09/grice.pdf

29
[Table 10 about here.]

[Table 11 about here.]

[Table 12 about here.]

7.2.2 Example 3: N=200 data based on the Pearl example

An example that fulfills the design of Table 9 with 100 subjects in the

control group and 100 in the treatment group is shown in Table 13.

[Table 13 about here.]

The Mplus input for a Bayes analysis of these data using probit is shown

in Appendix Section 14.6. The results are shown in Table 14. Bayesian

estimation allows for non-normal parameter distributions. As an example,

the posterior distribution for the ratio of the direct effect to the total effect

is shown in Figure 7.

[Table 14 about here.]

[Figure 7 about here.]

7.3 Binary mediator and continuous outcome

When the outcome is continuous instead of binary, the formulas of (40) -

(42) still apply by changing FY (x, m) to denote the expectation E(Y | X =

x, M = m). The expectation of Y is obtained for the various 0 and 1 values

of x and m indicated in the three formulas.

30
8 Mediation modeling with a nominal

mediator
Mediation modeling with a nominal mediator has apparently not been

approached in the SEM literature or in the causal mediation literature.

The question is how such mediation should be conceptualized. What does

it mean that a nominal variable acts as a mediator? As a hypothetical

example, consider an intervention aimed at reducing air pollution. An

important part of the intervention is to encourage people to change from

using their own car while commuting to work in favor of a van pool, bus,

or light rail. The mode of transportation mediator is therefore nominal. A

direct effect is also possible by the intervention also aiming to encourage

other low-pollution activities.

Here again, the general formulas of Section 4 can be used. The formulas

need the distribution of M conditional on X and the expectation of Y

conditional on M and X, followed by integration/summation over M. The

influence of X on M can be modeled by a multinomial logistic regression so

that the distribution of M conditional on X is well defined. The influence

of M on Y is naturally captured by different Y means for the different M

categories, by different Y=1 probabilities for a binary Y, or by different

rates for a count Y. Appendix Section 13.4 shows the causal effects for a

continuous outcome Y. The corresponding formulas for a binary or count

outcome Y follow in a straightforward way.

The joint analysis of a nominal variable as a dependent variable in one

regression and as an independent variable in another regression is easily

handled in Mplus by using a mixture analysis with a nominal latent class

31
variable that is the same as the observed nominal M. In this case, the latent

class membership is known, drawing on the Mplus KNOWNCLASS feature.

The Y means change over the classes as the default. An interaction between

X and M is captured by letting the direct influence of X on Y vary over the

latent classes. Maximum-likelihood estimation can be carried out for the

two regressions and the causal effects defined in MODEL CONSTRAINT

as before. The Mplus approach also allows for the nominal mediator to not

be observed but latent, or partly observed, or observed with error.

8.1 Monte Carlo simulation

A Monte Carlo simulation is carried out with n = 800 for a 3-category

mediator where the most polluting mode of transportation is the third

category. The Mplus input for Step 1 and Step 2 of the simulation are

shown in Section 14.7. The results are shown in Table 15, Table 16, and

Table 17. It is seen that the estimation performs very well. The direct

and indirect effects show good coverage. The Step 1 and Step 2 results

are slightly different due to latent class being unobserved in Step 1 and

observed in Step 2.

[Table 15 about here.]

[Table 16 about here.]

[Table 17 about here.]

32
8.2 Example 4: Hypothetical pollution data with

a nominal mediator and a binary outcome

Consider the hypothetical data in Table 18 as an example of the pollution

intervention with a binary outcome. The mediator category 3 corresponds

to using the car and has the highest pollution percentage.

[Table 18 about here.]

The Mplus input for this analysis is shown in Appendix Section 14.8.

The results are shown in Table 19 and Table 20.

[Table 19 about here.]

[Table 20 about here.]

9 Mediation modeling with a count out-

come
Causal effects using a count outcome are shown in Appendix Section 13.5.

A continuous mediator is considered, but as mentioned in the appendix

the count variable can also be a mediator. A count outcome can also be

combined with a binary or nominal mediator. To model the count variable,

Mplus can handle Poisson, negative binomial, and inflation versions of those

models as well as zero-truncation, hurdle modeling, and mixture (latent

class) versions.

Appendix Section 14.9 shows the Mplus input for a Monte Carlo

simulation study with a count outcome and a continuous mediator using

maximum-likelihood estimation. The results are shown in Table 21.

33
[Table 21 about here.]

10 Violated assumptions and sensitivity

analysis
As shown in the preceding sections, causally-derived direct and indirect

effects are not necessarily the same as SEM effects, particularly with non-

continuous mediators and/or outcomes. The causally-derived effects can,

however, be obtained via extended types of SEM analyses using Mplus. To

claim that effects are causal, however, it is not sufficient to simply use the

causally-derived effects. The set of assumptions given earlier needs to be

fulfilled for the effects to be causal and the plausibility of these assumptions

needs to be considered in each application. One way to read Holland (1988)

and Sobel (2008) is that the authors think many if not most applications

are not likely to fulfill such assumptions even in randomized studies. This

is also echoed in Bullock et al. (2010).

Imai et al. (2010a, b) stress the importance of sensitivity analysis as

part of mediation analysis. Techniques to study sensitivity to assumptions

have been proposed in Imai et al. (2010a, b) and VanderWeele (2010a).

This section focuses on the critical assumption of no mediator-outcome

confounding and shows how the sensitivity analysis proposed by Iamai et

al. is carried out in Mplus.

Consider the violation of the no mediator-outcome confounding in the

context of the simple mediation model of Figure 8. An unmeasured (latent)

variable Z influences both the mediator M and the outcome Y. When Z is

not included in the model, a covariance is created between the residuals in

34
the two equations of the regular mediation model as indicated in Figure 9.

Including the residual covariance, however, makes the model not identified.

An example of a mediator-outcome confounder in the aggressive behavior

example of Section 6.5 is the variable poverty which may affect both the

Grade 5 aggression score mediator and the juvenile court record outcome.

There are presumably many such omitted variables in a typical study.

Imai et al. (2010a, b) propose a sensitivity analysis where causal effects

are computed given different fixed values of the residual covariance. This

is useful both in real-data analyses as well as in planning studies. As for

the latter, the approach can answer questions such as how large does your

sample and effects have to be for the lower confidence band on the indirect

effect to not include zero when allowing for a certain degree of mediator-

outcome confounding?

As a first step in understanding the Imai et al. approach, Figure 10

indicates that there is another way to estimate the mediation model. The

figure shows that M and Y are regressed on X, allowing for a residual

covariance, but Y is not regressed on M. To illustrate this approach, a

Monte Carlo study is performed to show that the same estimates of the

indirect and direct effects are obtained as when regressing M on X and

regressing Y on M and X. Appendix Section 14.10.1 shows the Mplus input

for generating the data using the M on X, Y on M and X model, while

analyzing the data using the M on X, Y on X model of Figure 10. Table 22

shows the results, verifying that the data-generating parameters are well

recovered.

[Figure 8 about here.]

[Figure 9 about here.]

35
[Figure 10 about here.]

[Table 22 about here.]

As a second step in understanding the Imai et al. approach, Appendix

Section 13.6 shows how the parameters of the Figure 10 model can be used

to derive indirect and direct effects under different assumptions for the

residual covariance in the Figure 9 model. The coefficient β1 of the indirect

effect β1 γ1 is obtained as

p
β1 = σ/σ2 (ρ̃ − ρ (1 − ρ̃2 )/(1 − ρ2 )), (43)

where σ and σ2 are the standard deviations of the outcome and mediator

residuals in the Figure 10 model, ρ̃ is the correlation between these residuals,

and ρ is a sensitivity parameter representing the non-identified correlation

between the residuals of the Figure 9 model. The coefficient γ1 is obtained

from the regression of M on X. Appendix Section 13.6 shows that the direct

effect β2 is obtained as

β2 = κ1 − β1 γ1 , (44)

where κ1 is obtained from the regression of Y on X.

10.1 Sensitivity analysis in a Monte Carlo study

To illustrate the sensitivity analysis, Appendix Section 14.10.2 shows the

Mplus input for a Monte Carlo study that generates data according to

Figure 9 with a residual correlation of 0.25. The indirect effect is 0.25 and

the direct effect is 0.4. The data are analyzed by the model of Figure 10

using MODEL CONSTRAINT to derive the data-generating parameters

36
according to the appendix formulas while applying a fixed correlation of

ρ = 0.25, that is, the true correlation. Table 23 shows that the indirect

and direct effects (labeled ind and de) are correctly estimated with this

adjustment.

[Table 23 about here.]

A sensitivity analysis is obtained by varying the fixed ρ correlation

in MODEL CONSTRAINT. The above Monte Carlo study is used to

illustrate this. The correct value for the indirect effect is 0.25 (marked

with a horizontal broken line). The biased estimate assuming ρ = 0 is

0.3287, an overestimation due to ignoring the positive residual correlation.

The sensitivity analysis varies the ρ values from −0.9 to +0.9. A graph

of the indirect effect is shown in Figure 11, including a 95% confidence

interval. Using ρ = 0, the biased estimate of 0.3287 is obtained, that is,

no adjustment is made. Using the correct value of ρ = 0.25, the correct

indirect effect value of 0.25 is obtained. For lower ρ values the effect is

overestimated and for larger ρ values the effect is underestimated.

[Figure 11 about here.]

The graph provides useful information for planning new data collections.

At this sample size (n = 400) and effect size, the lower confidence limit does

not include zero until about ρ = 0.6. This means that a rather high degree

of confounding is needed for the effect to not be detected. Also, in the range

of ρ from about -0.1 to +0.4 the confidence interval covers the correct value

of 0.25 for the indirect effect.

These results are obtained by maximum-likelihood estimation using

regular standard errors and using symmetric confidence intervals due

37
to the assumption of a normal parameter estimate distribution for the

indirect effect. For smaller samples it may be better to use confidence

(credibility) intervals generated by Bayesian analysis, allowing for a non-

normal posterior for the indirect effect, producing non-symmetric confidence

intervals.

10.2 Example 5: Sensitivity analysis for head

circumference at birth and mother’s drinking and

smoking

This example considers the effects on the baby’s head circumference of

mother’s drinking and smoking during pregnancy (Day et al., 1994). A

reduction in head circumference is frequently used as a proxy for the

potential of deficient cognitive development in a child. The dependent

variables in the mediation model are baby’s head circumference at birth

(hcirc0) and at 36 months (hcirc36). The key focus is on a binary risk factor

defined by the mother’s drinking and smoking during the third trimester

(alcccig).

Figure 12 shows the mediation model. One may hypothesize that

mothers’ drinking and smoking during pregnancy affect babies’ head

circumference at birth, but any effect at 36 months is an indirect effect via

hcirc0. That is, if head circumference is low at 36 months it is because it is

low at birth. An alternative hypothesis is that a baby’s head circumference

at birth and 36 months are both directly affected by mother’s drinking and

smoking during pregnancy. That is, the growth rate in head circumference,

after the baby has left the womb, is affected by mother’s drinking and

38
smoking during pregnancy.

It should be emphasized that this is not a randomized study, so that

there are many possibilities for confounding. As a minimal set, gender

and ethnicity are added as covariates to be able to gauge the effects of

the mother’s behavior during pregnancy controlling for those variables. For

example, male babies tend to have a larger head circumference at birth than

female babies and males may also have a faster growth rate, hence impacting

both the mediator and the outcome. The baby’s gender is scored as 1 for

males and 0 for females, and baby’s ethnicity scored as 1 for blacks and 0

for others.

[Figure 12 about here.]

In line with the Imai et al. sensitivity approach, hcirc36 is regressed

on alccig, gender, and ethnicity and hcirc0 is regressed on alccig, gender,

and ethnicity. A first analysis uses a residual correlation ρ fixed at zero,

that is, carrying out a regular mediation analysis equivalent to that of

Figure 12. The Mplus input is given in Appendix Section 14.10.3. Table 24

shows the results. In the section New/additional parameters this gives

a significant indirect effect of −0.162 and an insignificant direct effect

of 0.084, both in standard deviation units for hcirc36. In terms of the

parameters of the original model of Figure 12, the estimate for β1 is

significant at 0.444, and the estimate of γ1 is found at the top of the

table under the regression of hcirc0 on alccig, namely −0.366. The β1 γ1

product is the reported indirect effect. The results indicate that mother’s

drinking and smoking are detrimental to the child’s head circumference

at birth, having an indirect effect also three years later, but having no

direct effect. A sensitivity analysis is, however, needed to study effects

39
of potential omitted mediator-outcome confounders. There are presumably

many omitted variables influencing head circumference at both birth and 36

months. It is likely that these omitted variables create a positive correlation

between the residuals of the mediator and the outcome.

[Table 24 about here.]

Figure 13 shows the results of the sensitivity analysis. The data for

the graph are produced by a series of analyses using the Mplus input in

Appendix Section 14.10.3, varying the ρ value of MODEL CONSTRAINT.

The figure shows that if the residual correlation ρ is less than about 0.4,

the negative indirect effect is still bounded away from zero. A residual

correlation as large as 0.4 or larger might, however, be considered quite

possible in this application. If so, the detrimental indirect causal effect of

mother’s drinking and smoking may not be convincingly demonstrated in

this case.

[Figure 13 about here.]

The direct effect also changes as a function of the residual correlation ρ

(see (44). Figure 14 shows that the direct effect is not significantly different

from zero in the range of ρ from -0.3 to 0.75. Assuming that the residual

correlation falls somewhere in this wide range, a direct effect is not detected.

[Figure 14 about here.]

11 General mediation modeling


The basic mediation models discussed so far are simple versions of what is

often seen in practice. This section lists a few of the generalizations and

40
outlines how the causally-defined effects come into play in these models.

11.1 Moderated mediation

The need to study moderated mediation frequently arises in applications.

Figure 1 of Section 2 is an example where the binary treatment variable X

moderates the influence of the mediator M on the outcome Y. An example

of moderation of the regression of M on X and the regression of Y on X is

shown in Figure 15, where the observed covariate Z is a moderator. Using

the aggressive behavior example of Section 6.5, the Grade 1 Fall aggression

score may serve as a moderator in that initially more aggressive boys are

somewhat more likely to benefit from the intervention. This is often referred

to as treatment-baseline interaction.

[Figure 15 about here.]

Figure 15 corresponds to the model

yi = β0 + β1 mi + β2 xi + β3 xi zi + 1i , (45)

mi = γ0 + γ1 xi + γ2 zi + γ3 xi zi + 2i , (46)

Applying the Appendix Section 13.1 formulas, it follows that the direct and

total indirect effects are

DE = β2 + β3 z, (47)

T IE = β1 (γ1 + γ3 z). (48)

The effects can then be evaluated at different z values of interest.

41
For a binary moderator, multiple-group SEM gives a flexible approach.

Again using the aggressive behavior example, females have less of an effect of

the intervention than boys. The multiple-group approach can estimate the

same parameters as in (45) and (46), leading to the same effect definitions,

but also allows further flexibility such as group-varying residual variances.

11.2 Mediation analysis with latent variables

In a more general setting, latent variables may often play the roles of

mediators and outcomes. The latent variables may represent continuous

latent response variables, continuous factors, or categorical latent class

variables.

11.2.1 Latent response variables: Latent versus observed


binary and ordinal mediators and outcomes

In the smoking example of Section 6.6, the analyses compared treating

the mediator as an observed variable versus a latent response variable, or

response tendency, m∗ behind an ordered categorical (ordinal) observed

variable. Similarly, a binary mediator can be treated as either the

observed binary variable or as the latent continuous response variable. The

substantively relevant mediator may be the response tendency or the actual

manifestation. This same line of thinking applies to the outcome. For

example, the causal effects for an ordinal outcome can be expressed by the

causal formulas in terms of the expectation of this observed categorical

variable, where an intervention attempts to increase or decrease the

probabilities of certain observed categories. Or, the substantively relevant

outcome may be the response tendency, where the observed categories are

42
merely crude categorizations of this tendency. The choice decides if the

causal effects for continuous or categorical variables should be used.

11.2.2 Factors

Figure 16 shows an example of factors measured by multiple indicators.

In this case, the causally-defined effects pertain to the continuous latent

mediator fm and the continuous latent outcome fy, that is, the usual

formulas for continuous variables apply. Adding moderated mediation

implies modeling with interactions involving latent variables, which is

available in Mplus using maximum-likelihood estimation.

[Figure 16 about here.]

11.2.3 Latent class variables

Figure 17 shows an example where the mediator is a latent class variable

measured by multiple indicators. The multiple indicators may correspond

to repeated measures with random effects (i and s) as in growth mixture

modeling (Muthén & Asparouhov, 2009). In these cases, the mediator

is nominal and the formulas of Section 8 apply. This involves mixture

analysis, which is available in Mplus using maximum-likelihood or Bayesian

estimation.

[Figure 17 about here.]

11.3 Multilevel mediation

Causal inference in multilevel settings presents further challenges for

mediational modeling and is beyond the scope of this paper. Additional

43
assumptions are needed for causally-defined effects. Key references include

Hong and Raudenbush (2006) and VanderWeele (2010b).

12 Conclusions
This paper summarizes some of the literature on causal effects in mediation

analysis. Applications are shown where the effects are estimated using

Mplus. This broadens mediation analysis as currently carried out in

SEM practice, where causal effects have been considered only in the

case of continuous mediators and outcomes. In this paper, causal

effects are computed also for mediators and outcomes that are binary,

ordinal, nominal, or count variables. The causal effects require strong

assumptions even in randomized designs, especially sequential ignorability,

which is presumably often violated to some extent due to mediator-outcome

confounding. To study the effects of violating this assumption, it is shown

how a sensitivity analysis developed by Imai et al. (2010a,b) can be carried

out using Mplus. This can be used both in planning a new study and in

evaluating the results of an existing study.

Reports on SEM analyses often use language to interpret their findings

which implies that the effects found are causal. The causal effects literature

indicates how difficult it can be for such claims to be correct. It is likely

that more often only approximations to causal findings are obtained. In this

sense, SEM mediation analysis perhaps serves more as a useful exploratory

tool rather than a confirmatory causal analysis device, as is sometimes

claimed.

Ongoing research on the mediation topic focuses on the Achilles heel of

44
the analysis, namely that the mediator is not randomized. To avoid this,

new designs are explored, such as parallel designs, encouragement designs,

and crossover designs; see, e.g., Bullock et al. (2010) and Imai et al (2011).

These designs, however, come with their own challenges and assumptions

and much further research is needed.

45
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[2] Bollen, K. A. (1989). Structural equation models with latent variables.

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[3] Bullock, J.G., Green, D.P. & Ha, S.E. (2010). Yes, but what’s the

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Social Psychology, 98, 550-558.

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65
List of Figures
1 A mediation model with treatment-mediator interaction. The filled
circle represents an interaction term consisting of the variables
connected to it without arrow heads, in this case x and m. . . . . 67
2 Latent response variable m∗ behind a three-category ordinal vari-
able m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3 Bayes posterior distribution for the direct effect odds ratio . . . . 69
4 Bayes posterior distribution for the total indirect effect odds ratio 70
5 A mediation model for aggressive behavior and juvenile court outcome 71
6 A mediation model for intentions to stop smoking . . . . . . . . . 72
7 Bayes posterior distribution for the ratio of the direct effect to the
total effect for n=200 data based on Pearl . . . . . . . . . . . . . 73
8 Mediator-outcome confounding 1 . . . . . . . . . . . . . . . . . . 74
9 Mediator-outcome confounding 2 . . . . . . . . . . . . . . . . . . 75
10 Mediator-outcome confounding 3 . . . . . . . . . . . . . . . . . . 76
11 Indirect effect based on sensitivity analysis with ρ varying from -0.9
to +0.9 and true residual correlation 0.25 . . . . . . . . . . . . . . 77
12 Mediation model for mother’s drinking and smoking related to
child’s head circumference . . . . . . . . . . . . . . . . . . . . . . 78
13 Sensitivity analysis for indirect effect of head circumference example 79
14 Sensitivity analysis for direct effect of head circumference example 80
15 Z moderating the effect of X on M and Y . . . . . . . . . . . . . . 81
16 Continuous latent factors as mediator and outcome . . . . . . . . 82
17 Latent class variable as mediator . . . . . . . . . . . . . . . . . . 83

66
Figure 1: A mediation model with treatment-mediator interaction. The filled
circle represents an interaction term consisting of the variables connected to it
without arrow heads, in this case x and m.

67
Figure 2: Latent response variable m∗ behind a three-category ordinal variable m

68
Figure 3: Bayes posterior distribution for the direct effect odds ratio

69
Figure 4: Bayes posterior distribution for the total indirect effect odds ratio

70
Figure 5: A mediation model for aggressive behavior and juvenile court outcome

71
Figure 6: A mediation model for intentions to stop smoking

72
Figure 7: Bayes posterior distribution for the ratio of the direct effect to the total
effect for n=200 data based on Pearl

73
Figure 8: Mediator-outcome confounding 1

74
Figure 9: Mediator-outcome confounding 2

75
Figure 10: Mediator-outcome confounding 3

76
Figure 11: Indirect effect based on sensitivity analysis with ρ varying from -0.9 to
+0.9 and true residual correlation 0.25

Indirect effect

1.6

1.4

1.2

.8

.6

.4

.2
ρ

−1 −.75 −.5 −.25 −.2 .25 .5 .75 1

−.4

−.6

77
Figure 12: Mediation model for mother’s drinking and smoking related to child’s
head circumference

78
Figure 13: Sensitivity analysis for indirect effect of head circumference example

Indirect effect

.75

.5

.25
ρ

−1 −.75 −.5 −.25 −.25 .25 .5 .75 1

−.5

−.75

−1

−1.25

−1.5

79
Figure 14: Sensitivity analysis for direct effect of head circumference example

Direct effect

1.2

.8

.6

.4

.2
ρ

−1 −.75 −.5 −.25 −.2 .25 .5 .75 1

−.4

−.6

−.8

−1

−1.2

80
Figure 15: Z moderating the effect of X on M and Y

81
Figure 16: Continuous latent factors as mediator and outcome

82
Figure 17: Latent class variable as mediator

83
List of Tables
1 Output for continuous mediator, continuous outcome with treatment-
mediator interaction, Step 2 . . . . . . . . . . . . . . . . . . . . . 87
2 Output for Monte Carlo simulation with a binary outcome and a
continuous mediator, n = 200, Step 2, ML . . . . . . . . . . . . . 88
3 Output for Monte Carlo simulation with a binary outcome and a
continuous mediator, n = 200, Step 2, Bayes . . . . . . . . . . . . 89
4 Output for aggressive behavior and juvenile court record using probit 90
5 Output for aggressive behavior and juvenile court record using logit 91
6 Intentions to stop smoking data (Source: MacKinnon et al., 2007,
Clinical Trials, 4, p. 510) . . . . . . . . . . . . . . . . . . . . . . . 92
7 Output for intentions to stop smoking using probit with the
mediator treated as an observed continuous variable using ML . . 93
8 Output for intentions to stop smoking using probit with the
mediator treated as a latent continuous variable using WLSMV . 94
9 Pearl’s hypothetical binary case (Source: Pearl, 2010, 2011) . . . . 95
10 Output for Pearl’s hypothetical binary case using logit with ML,
Step 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
11 Output for Pearl’s hypothetical binary case using probit with ML,
Step 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
12 Output for Pearl’s hypothetical binary case using probit with
Bayes, Step 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
13 Pearl data n=200 . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
14 Output for n=200 data based on the Pearl example . . . . . . . . 100
15 Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 1 . . . . . . . . . . . . . . . . . . . . . 101
16 Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 2, part 1 . . . . . . . . . . . . . . . . . 102
17 Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 2, part 2 . . . . . . . . . . . . . . . . . 103
18 Hypothetical pollution data with a nominal mediator and a binary
outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
19 Output for hypothetical pollution data with a nominal mediator
and a binary outcome, part 1 . . . . . . . . . . . . . . . . . . . . 105
20 Output for hypothetical pollution data with a nominal mediator
and a binary outcome, part 2 . . . . . . . . . . . . . . . . . . . . 106
21 Output for mediation modeling with a count outcome, Step 2 . . 107
22 Output for Monte Carlo simulation, analyzing by M and Y
regressed on X only . . . . . . . . . . . . . . . . . . . . . . . . . . 108

84
23 Output for generating data with true residual correlation 0.25 and
analyzing data with Imai’s ρ fixed at the true value 0.25 . . . . . 109
24 Output for head circumference analysis using the Imai et al.
sensitivity approach with ρ = 0 . . . . . . . . . . . . . . . . . . . 110
25 Input for step 1 y on xm . . . . . . . . . . . . . . . . . . . . . . . 111
26 Input for step 2 y on xm . . . . . . . . . . . . . . . . . . . . . . . 112
27 Input for step 1 ML y on xm n=200 . . . . . . . . . . . . . . . . . 113
28 Input for step 2 ML y on xm n=200 . . . . . . . . . . . . . . . . . 114
29 Input excerpts for step 2 bayes y on xm n=200 . . . . . . . . . . . 115
30 Input for 1st rep step 2 bayes y on xm n=200 . . . . . . . . . . . 116
31 Input excerpts for juvcrt on agg5 on tx agg1 tx-agg5 probit . . . . 117
32 Input for juvcrt on agg5 on tx agg1 tx-agg5 probit, continued . . 118
33 Input for juvcrt on agg5 on tx agg1 tx-agg5 logit . . . . . . . . . . 119
34 Input for m cont probit using maximum-likelihood . . . . . . . . . 120
35 Input for m* cont probit using weighted least-squares . . . . . . . 121
36 Input for step 1 binary m binary y logit with xm interaction pearl
ex n=400 tie and pie . . . . . . . . . . . . . . . . . . . . . . . . . 122
37 Input for step 1 binary m binary y logit with xm interaction pearl
ex n=400 tie and pie, continued . . . . . . . . . . . . . . . . . . . 123
38 Input for step 2 define xm binary m binary y logit with xm
interaction pearl ex n=400 tie and pie . . . . . . . . . . . . . . . . 124
39 Input for step 1 binary m binary y probit with xm interaction pearl
ex n=400 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
40 Input for step 1 binary m binary y probit with xm interaction pearl
ex n=400, continued . . . . . . . . . . . . . . . . . . . . . . . . . 126
41 Input for step 2 ml define xm binary m binary y probit with xm
interaction pearl ex n=400 . . . . . . . . . . . . . . . . . . . . . . 127
42 Input for step 2 bayes define xm binary m binary probit with xm
interaction pearl ex n=400 10k . . . . . . . . . . . . . . . . . . . 128
43 Input for step 2 bayes define xm binary m binary probit with xm
interaction pearl ex n=400 10k, continued . . . . . . . . . . . . . 129
44 Input for Bayes analysis of n=200 data drawn on the Pearl example 130
45 Input for Bayes analysis of n=200 data drawn on the Pearl example,
continued . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
46 Input for step 1 y on xm n=800 . . . . . . . . . . . . . . . . . . . 132
47 Input for step 1 y on xm n=800, continued . . . . . . . . . . . . . 133
48 Input for step 2 y on xm knownclass . . . . . . . . . . . . . . . . 134
49 Input for step 2 y on xm knownclass, continued . . . . . . . . . . 135
50 Input for hypothetical pollution data with a nominal mediator and
a binary outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

85
51 Input for hypothetical pollution data with a nominal mediator and
a binary outcome, continued . . . . . . . . . . . . . . . . . . . . . 137
52 Input for step 1 count y on xm . . . . . . . . . . . . . . . . . . . 138
53 Input for step 1 count y on xm, continued . . . . . . . . . . . . . 139
54 Input for step 2 count y on xm . . . . . . . . . . . . . . . . . . . 140
55 Input for rho=0 run: replicating regular mediation analysis . . . . 141
56 Input for true corr=0.25, rho=0.25 . . . . . . . . . . . . . . . . . 142
57 Input excerpts for head circumference analysis with rho=0 corre-
sponding to regular mediation analysis . . . . . . . . . . . . . . . 143

86
Table 1: Output for continuous mediator, continuous outcome with treatment-
mediator interaction, Step 2

Estimates S.E. M.S.E. 95% % Sig


Population Average Std. Dev. Average Cover Coeff

y ON
x 0.400 0.4011 0.1784 0.1761 0.0318 0.950 0.616
xm 0.000 0.2006 0.0716 0.0711 0.0051 0.958 0.780
m 0.500 0.5006 0.0493 0.0501 0.0024 0.964 1.000
m ON
x 0.500 0.5015 0.0981 0.0997 0.0096 0.940 0.998
Intercepts
y 1.000 0.9984 0.1107 0.1122 0.0122 0.954 1.000
m 2.000 2.0032 0.0683 0.0705 0.0047 0.962 1.000
Residual variances
y 0.500 0.4974 0.0372 0.0352 0.0014 0.936 1.000
m 1.000 0.9933 0.0667 0.0702 0.0045 0.960 1.000
New/additional parameters
tie 0.350 0.3518 0.0748 0.0745 0.0056 0.932 0.998
pie 0.250 0.2509 0.0544 0.0561 0.0029 0.950 0.998
de 0.800 0.8027 0.0802 0.0766 0.0064 0.936 1.000

87
Table 2: Output for Monte Carlo simulation with a binary outcome and a
continuous mediator, n = 200, Step 2, ML

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

y ON
x 0.300 0.2740 0.2796 0.2770 0.0787 0.952 0.194
m 0.700 0.7138 0.1848 0.1799 0.0343 0.956 0.990
xm 0.200 0.2370 0.2865 0.2842 0.0833 0.954 0.110
m ON
x 0.500 0.4894 0.1207 0.1223 0.0146 0.942 0.972
Intercepts
m 0.500 0.5044 0.0863 0.0861 0.0074 0.970 1.000
Thresholds
y$1 0.500 0.5058 0.1670 0.1672 0.0279 0.952 0.880
Residual variances
m 0.750 0.7465 0.0808 0.0746 0.0065 0.920 1.000
New/additional parameters
ind 0.450 0.4661 0.1621 0.1600 0.0265 0.948 0.950
dir 0.450 0.3935 0.2140 0.2122 0.0458 0.952 0.462
arg11 0.700 0.7134 0.1858 0.1819 0.0346 0.962 0.992
arg10 0.250 0.2473 0.1846 0.1807 0.0340 0.950 0.304
arg01 0.200 0.2037 0.1788 0.1699 0.0319 0.942 0.218
arg00 -0.150 -0.1462 0.1546 0.1489 0.0239 0.948 0.188
v1 1.607 1.7107 0.3486 0.3263 0.1319 0.948 1.000
v0 1.367 1.4057 0.2238 0.1998 0.0515 0.942 1.000
probit11 0.552 0.5484 0.1317 0.1327 0.0173 0.952 0.992
probit10 0.197 0.1948 0.1468 0.1442 0.0215 0.946 0.260
probit01 0.171 0.1678 0.1437 0.1383 0.0206 0.942 0.240
probit00 -0.128 -0.1244 0.1315 0.1256 0.0173 0.952 0.190
tie 0.131 0.1303 0.0391 0.0388 0.0015 0.946 0.958
de 0.129 0.1255 0.0689 0.0676 0.0047 0.952 0.450
pie 0.119 0.1151 0.0358 0.0632 0.0013 0.936 0.950

88
Table 3: Output for Monte Carlo simulation with a binary outcome and a
continuous mediator, n = 200, Step 2, Bayes

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

y ON
x 0.300 0.2677 0.2760 0.2762 0.0771 0.954 0.188
m 0.700 0.7126 0.1830 0.1812 0.0336 0.950 0.990
xm 0.200 0.2513 0.2841 0.2869 0.0832 0.958 0.128
m ON
x 0.500 0.4897 0.1207 0.1240 0.0147 0.946 0.968
Intercepts
m 0.500 0.5044 0.0863 0.0875 0.0075 0.972 1.000
Thresholds
y$1 0.500 0.5062 0.1655 0.1656 0.0274 0.950 0.886
Residual variances
m 0.750 0.7650 0.0828 0.0777 0.0071 0.926 1.000
New/additional parameters
ind 0.450 0.4616 0.1629 0.1664 0.0266 0.956 0.966
dir 0.400 0.3961 0.2133 0.2134 0.0454 0.956 0.452
arg11 0.700 0.7204 0.1879 0.1851 0.0357 0.946 0.992
arg10 0.250 0.2510 0.1851 0.1818 0.0342 0.944 0.296
arg01 0.200 0.2012 0.1785 0.1714 0.0318 0.940 0.234
arg00 -0.150 -0.1460 0.1544 0.1500 0.0238 0.946 0.194
v1 1.607 1.7456 0.3648 0.3644 0.1519 0.940 1.000
v0 1.367 1.4134 0.2252 0.2157 0.0527 0.954 1.000
probit11 0.552 0.5465 0.1305 0.1312 0.0170 0.952 0.992
probit10 0.197 0.1949 0.1451 0.1421 0.0210 0.946 0.296
probit01 0.171 0.1645 0.1427 0.1376 0.0204 0.940 0.234
probit00 -0.128 -0.1234 0.1305 0.1250 0.0170 0.946 0.194
tie 0.131 0.1266 0.0385 0.0387 0.0015 0.950 0.966
de 0.129 0.1245 0.0673 0.0665 0.0045 0.954 0.468
pie 0.119 0.1106 0.0352 0.0363 0.0013 0.956 0.960
ortie 1.779 1.7858 0.3050 0.3211 0.0929 0.944 1.000
orde 1.681 1.7321 0.4935 0.5272 0.2457 0.956 1.000
orpie 1.614 1.5914 0.2379 0.2553 0.0570 0.958 1.000
89
Table 4: Output for aggressive behavior and juvenile court record using probit

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-Value

juvcrt ON
tx 0.003 0.192 0.013 0.990
agg5 0.451 0.103 4.374 0.000
xm 0.263 0.231 1.140 0.254
agg1 -0.003 0.096 -0.036 0.972
agg5 ON
tx -0.267 0.115 -2.325 0.020
agg1 0.462 0.060 7.730 0.000
Intercepts
agg5 0.074 0.070 1.054 0.292
Thresholds
juvcrt$1 -0.035 0.097 -0.364 0.716
Residual variances
agg5 0.787 0.074 10.706 0.000
New/additional parameters
ind -0.191 0.096 -1.983 0.047
dir 0.022 0.197 0.111 0.911
arg11 -0.100 0.174 -0.576 0.565
arg10 0.090 0.176 0.514 0.607
arg00 0.069 0.102 0.672 0.502
v1 1.401 0.247 5.664 0.000
v0 1.160 0.076 15.310 0.000
probit11 -0.085 0.147 -0.574 0.566
probit10 0.076 0.147 0.521 0.602
probit00 0.064 0.095 0.673 0.501
indirect -0.064 0.030 -2.158 0.031
direct 0.005 0.067 0.076 0.940
orind 0.773 0.092 8.371 0.000
ordir 1.021 0.275 3.714 0.000

90
Table 5: Output for aggressive behavior and juvenile court record using logit

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-Value

juvcrt ON
tx 0.002 0.316 0.006 0.995
agg5 0.726 0.171 4.237 0.000
xm 0.431 0.393 1.096 0.273
agg1 0.000 0.159 -0.002 0.998
agg5 ON
tx -0.267 0.115 -2.325 0.020
agg1 0.462 0.060 7.730 0.000
Intercepts
agg5 0.074 0.070 1.054 0.292
Thresholds
juvcrt$1 -0.059 0.160 -0.366 0.714
Residual variances
agg5 0.787 0.074 10.706 0.000
New/additional parameters
ind -0.309 0.158 -1.957 0.050
dir 0.034 0.325 0.103 0.918
oddsrat 0.734 0.116 6.334 0.000

91
Table 6: Intentions to stop smoking data (Source: MacKinnon et al., 2007, Clinical
Trials, 4, p. 510)

Cigarette use
Intention No Use Use Total
4 (Yes) 9 20 29
3 (Probably) 14 20 34
Ctrl
2 (Don’t think so) 36 13 49
1 (No) 229 30 259
4 (Yes) 9 19 28
3 (Probably) 15 11 26
Tx
2 (Don’t think so) 43 11 54
1 (No) 353 32 385

92
Table 7: Output for intentions to stop smoking using probit with the mediator
treated as an observed continuous variable using ML

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-Value

ciguse ON
tx -0.203 0.109 -1.867 0.062
intent 0.538 0.048 11.227 0.000
intent ON
tx -0.186 0.070 -2.664 0.008
Intercepts
intent 0.106 0.056 1.906 0.057
Thresholds
ciguse$1 0.912 0.080 11.432 0.000
Residual variances
intent 0.990 0.069 14.291 0.000
New/additional parameters
ind -0.100 0.038 -2.602 0.009
dir -0.203 0.109 -1.867 0.062
arg11 -1.158 0.079 -14.579 0.000
arg10 -1.058 0.081 -13.072 0.000
arg00 -0.855 0.085 -10.105 0.000
v1 1.287 0.055 23.545 0.000
v0 1.287 0.055 23.545 0.000
probit11 -1.021 0.072 -14.240 0.000
probit10 -0.933 0.075 -12.514 0.000
probit00 -0.754 0.076 -9.947 0.000
indirect -0.022 0.009 -2.548 0.011
direct -0.050 0.027 -1.853 0.064
orind 0.853 0.051 16.587 0.000
ordir 0.731 0.123 5.941 0.000

93
Table 8: Output for intentions to stop smoking using probit with the mediator
treated as a latent continuous variable using WLSMV

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-Value

ciguse ON
tx -0.131 0.093 -1.409 0.159
intent 0.631 0.042 15.114 0.000
intent ON
tx -0.246 0.089 -2.756 0.006

Thresholds
ciguse$1 0.760 0.072 10.496 0.000
intent$1 0.525 0.067 7.849 0.000
intent$2 0.970 0.071 13.581 0.000
intent$3 1.378 0.082 16.721 0.000
New/additional parameters
ind -0.155 0.057 -2.711 0.007
dir -0.131 0.093 -1.409 0.159
arg11 -1.045 0.069 -15.102 0.000
arg10 -0.890 0.078 -11.443 0.000
arg00 -0.760 0.072 -10.496 0.000
v1 1.398 0.053 26.557 0.000
v0 1.398 0.053 26.557 0.000
probit11 -0.884 0.062 -14.195 0.000
probit10 -0.753 0.070 -10.727 0.000
probit00 -0.643 0.063 -10.189 0.000
indirect -0.037 0.014 -2.645 0.008
direct -0.035 0.024 -1.410 0.158
orind 0.796 0.066 12.037 0.000
ordir 0.829 0.111 7.454 0.000

94
Table 9: Pearl’s hypothetical binary case (Source: Pearl, 2010, 2011)

Treatment Enzyme Percentage Cured


X M Y=1

1 1 FY (1, 1) = 80%
1 0 FY (1, 0) = 40%
0 1 FY (0, 1) = 30%
0 0 FY (0, 0) = 20%

Treatment Percentage
X M=1

0 FM (0) = 40%
1 FM (1) = 75%

95
Table 10: Output for Pearl’s hypothetical binary case using logit with ML, Step
2

Estimates S.E. M.S.E. 95% % Sig


Population Average Std. Dev. Average Cover Coeff

m ON
x 1.504 1.5144 0.2193 0.2191 0.0481 0.964 1.000
y ON
x 0.981 1.0020 0.3741 0.3745 0.1401 0.958 0.774
m 0.539 0.5405 0.3446 0.3399 0.1185 0.952 0.340
xm 1.253 1.2701 0.4816 0.4953 0.2318 0.968 0.750
Thresholds
y$1 1.386 1.4085 0.2366 0.2315 0.0564 0.962 1.000
m$1 0.405 0.4136 0.1423 0.1449 0.0203 0.948 0.822
New/additional parameters
fm0 0.400 0.3986 0.0338 0.0346 0.0011 0.940 1.000
fm1 0.750 0.7490 0.0318 0.0306 0.0010 0.938 1.000
fy00 0.200 0.1991 0.0363 0.0362 0.0013 0.950 1.000
fy10 0.400 0.4018 0.0692 0.0690 0.0048 0.954 1.000
fy01 0.300 0.2981 0.0489 0.0510 0.0024 0.954 1.000
fy11 0.800 0.8009 0.0312 0.0325 0.0010 0.956 1.000
de 0.320 0.3222 0.0543 0.0539 0.0030 0.944 1.000
pie 0.035 0.0348 0.0229 0.0227 0.0005 0.950 0.296
tie 0.140 0.1399 0.0329 0.0329 0.0011 0.940 1.000
te 0.460 0.4621 0.0435 0.0442 0.0019 0.950 1.000
iete 0.070 0.0761 0.0501 0.0505 0.0025 0.962 0.272
dete 0.696 0.6945 0.0778 0.0762 0.0060 0.938 1.000
compdete 0.304 0.3055 0.0778 0.0762 0.0060 0.938 1.000
tiete 0.304 0.3055 0.0778 0.0762 0.0060 0.938 1.000

96
Table 11: Output for Pearl’s hypothetical binary case using probit with ML, Step
2

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

m ON
x 0.929 0.9341 0.1321 0.1321 0.0174 0.962 1.000
y ON
x 0.586 0.5973 0.2242 0.2244 0.0503 0.958 0.766
m 0.315 0.3148 0.2008 0.1990 0.0402 0.952 0.336
xm 0.779 0.7866 0.2857 0.2943 0.0815 0.968 0.794
Thresholds
y$1 0.840 0.8506 0.1339 0.1315 0.0180 0.956 1.000
m$1 0.254 0.2588 0.0883 0.0899 0.0078 0.0946 0.824
New/additional parameters
de 0.320 0.3216 0.0543 0.0539 0.0029 0.946 1.000
tie 0.140 0.1399 0.0329 0.0329 0.0011 0.938 1.000
pie 0.035 0.0347 0.0229 0.0227 0.0005 0.950 0.294
te 0.460 0.4615 0.0434 0.0442 0.0019 0.950 1.000
tiete 0.304 0.3060 0.0780 0.0764 0.0061 0.942 1.000
piete 0.070 0.0758 0.0501 0.0506 0.0025 0.964 0.272
dete 0.696 0.6940 0.0780 0.0764 0.0061 0.942 1.000
compdete 0.304 0.3060 0.0780 0.0764 0.0061 0.942 1.000
pfm0 0.400 0.3983 0.0339 0.0345 0.0011 0.940 1.000
pfm1 0.750 0.7492 0.0319 0.0306 0.0010 0.938 1.000
pfy00 0.200 0.1996 0.0364 0.0363 0.0013 0.950 1.000
pfy10 0.400 0.4017 0.0692 0.0690 0.0048 0.954 1.000
pfy01 0.300 0.2980 0.0488 0.0511 0.0024 0.956 1.000
pfy11 0.800 0.8003 0.0312 0.0326 0.0010 0.956 1.000

97
Table 12: Output for Pearl’s hypothetical binary case using probit with Bayes,
Step 2

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

m ON
x 0.929 0.9334 0.1318 0.1310 0.0174 0.958 1.000
y ON
x 0.586 0.5963 0.2204 0.2241 0.0486 0.958 0.772
m 0.315 0.3110 0.1976 0.1993 0.0390 0.954 0.330
xm 0.779 0.7916 0.2792 0.2919 0.0780 0.970 0.808
Thresholds
y$1 0.840 0.8481 0.1320 0.1308 0.0175 0.952 1.000
m$1 0.254 0.2581 0.0881 0.0894 0.0078 0.946 0.824
New/additional parameters
de 0.320 0.3208 0.0536 0.0537 0.0029 0.956 1.000
tie 0.140 0.1371 0.0323 0.0324 0.0011 0.946 1.000
pie 0.035 0.0334 0.0221 0.0227 0.0005 0.958 0.330
te 0.460 0.4598 0.0431 0.0441 0.0019 0.958 1.000
tiete 0.304 0.3027 0.0773 0.0770 0.0060 0.946 0.330
piete 0.070 0.0735 0.0488 0.0518 0.0024 0.956 1.000
dete 0.696 0.6972 0.0773 0.0770 0.0060 0.946 1.000
compdete 0.304 0.3027 0.0773 0.0770 0.0060 0.946 1.000
orde 4.030 4.2200 1.0343 1.1117 1.1036 0.950 1.000
ortie 1.833 1.8375 0.2559 0.2614 0.0654 0.954 1.000
pfm0 0.500 0.3986 0.0338 0.0342 0.0114 0.176 1.000
pfm1 0.500 0.7492 0.0319 0.0303 0.0631 0.000 1.000
pfy00 0.500 0.2002 0.0360 0.0361 0.0912 0.000 1.000
pfy10 0.500 0.4021 0.0688 0.0681 0.0143 0.712 1.000
pfy01 0.500 0.2974 0.0485 0.0507 0.0434 0.034 1.000
pfy11 0.500 0.8008 0.0312 0.0319 0.0915 0.000 1.000
numde 0.500 0.5614 0.0461 0.0453 0.0059 0.730 1.000
dende 0.500 0.2400 0.0288 0.0299 0.0684 0.000 1.000
numtie 0.500 0.7008 0.0319 0.0320 0.0413 0.000 1.000
dentie 0.500 0.5614 0.0461 0.0453 0.0059 0.730 1.000

98
Table 13: Pearl data n=200

X M Y
Total
Not Cured Cured
Enzyme Absent 48 12 60
Ctrl
Enzyme Present 28 12 40
Enzyme Absent 15 10 25
Tx
Enzyme Present 15 60 75

99
Table 14: Output for n=200 data based on the Pearl example

Posterior One-Tailed 95% C.I.


Parameter Estimate S.D. P-Value Lower 2.5% Upper 2.5%

m ON
x 0.960 0.187 0.000 0.598 1.325
y ON
x 0.596 0.314 0.031 -0.030 1.212
m 0.328 0.259 0.103 -0.179 0.843
xm 0.757 0.406 0.031 -0.030 1.553
Thresholds
y$1 0.709 0.170 0.000 0.378 1.051
m$1 0.232 0.122 0.028 -0.005 0.469
New/additional parameters
de 0.322 0.077 0.000 0.168 0.470
tie 0.131 0.046 0.000 0.051 0.231
pie 0.038 0.033 0.103 -0.021 0.111
te 0.456 0.061 0.000 0.332 0.569
tiete 0.288 0.113 0.000 0.109 0.547
piete 0.084 0.076 0.103 -0.047 0.258
dete 0.712 0.113 0.000 0.453 0.891
compdete 0.288 0.113 0.000 0.109 0.547
pfm0 0.408 0.047 0.000 0.319 0.502
pfm1 0.767 0.043 0.000 0.674 0.844
pfy00 0.239 0.052 0.000 0.147 0.353
pfy10 0.455 0.102 0.000 0.259 0.658
pfy01 0.351 0.071 0.000 0.221 0.497
pfy11 0.834 0.044 0.000 0.735 0.906
numde 0.609 0.066 0.000 0.477 0.736
dende 0.285 0.043 0.000 0.208 0.376
orde 3.908 1.508 0.000 2.024 7.852
numind 0.744 0.045 0.000 0.649 0.825
denind 0.609 0.066 0.000 0.477 0.736
orind 1.841 0.398 0.000 1.290 2.831

100
Table 15: Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 1

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

Latent class 1
y ON
x -0.500 -0.4884 0.2647 0.2461 0.0701 0.936 0.546
Intercepts
y -2.000 -2.0254 0.2186 0.2050 0.0483 0.946 0.998
Residual variances
y 0.750 0.7420 0.0776 0.0739 0.0061 0.920 1.000
Latent class 2
y ON
x -0.300 -0.3037 0.3664 0.3472 0.1340 0.934 0.180
Intercepts
y 0.000 0.0107 0.2900 0.2651 0.0840 0.918 0.082
Residual variances
y 0.750 0.7420 0.0776 0.0739 0.0061 0.920 1.000
Latent class 3
y ON
x -0.200 -0.2000 0.1675 0.1609 0.0280 0.938 0.254
Intercepts
y 2.000 2.0155 0.1260 0.1173 0.0161 0.938 1.000
Residual variances
y 0.750 0.7420 0.0776 0.739 0.0061 0.920 1.000
Categorical latent variables
c#1 ON
x 0.700 0.7059 0.4183 0.3374 0.1746 0.950 0.526
c#2 ON
101
x 0.300 0.2761 0.3466 0.3321 0.1205 0.944 0.134
Intercepts
c#1 -1.000 -1.0041 0.3520 0.3067 0.1237 0.956 0.900
c#2 -0.500 -0.4559 0.2599 0.2513 0.0694 0.956 0.512
Table 16: Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 2, part 1

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

Latent class 1
y ON
x -0.500 -0.5045 0.1332 0.1285 0.0177 0.944 0.972
Intercepts
y -2.000 -2.0007 0.1011 0.1001 0.0102 0.958 1.000
Residual variances
y 0.750 0.7465 0.0360 0.0373 0.0013 0.954 1.000
Latent class 2
y ON
x -0.300 -0.2976 0.1125 0.1093 0.0126 0.942 0.772
Intercepts
y 0.000 0.0021 0.0799 0.0780 0.0064 0.944 0.056
Thresholds
Residual variances
y 0.750 0.7465 0.0360 0.0373 0.0013 0.954 1.000
Latent class 3
y ON
x -0.200 -0.1948 0.0917 0.0923 0.0084 0.954 0.554
Intercepts
y 2.000 2.0002 0.0629 0.0609 0.0039 0.936 1.000
Residual variances
y 0.750 0.7465 0.0360 0.0373 0.0013 0.954 1.000

102
Table 17: Output for Monte Carlo simulation of a nominal mediator and a
continuous outcome, Step 2, part 2

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

Categorical latent variables


c#1 ON
x 0.700 0.6916 0.1667 0.1832 0.0278 0.966 0.982
c#2 ON
x 0.300 0.2982 0.1693 0.1656 0.0286 0.946 0.426
Intercepts
c#1 -1.000 -0.9920 0.1233 0.1357 0.0152 0.962 1.000
c#2 -0.500 -0.4950 0.1142 0.1146 0.0130 0.966 0.998
New/additional parameters
denom0 1.974 1.9872 0.0950 0.0989 0.0092 0.964 1.000
denom1 2.559 2.5729 0.1614 0.1617 0.0262 0.966 1.000
p10 0.186 0.1877 0.0178 0.0195 0.0003 0.970 1.000
p11 0.289 0.2892 0.0216 0.0226 0.0005 0.964 1.000
p20 0.307 0.3080 0.0230 0.0231 0.0005 0.954 1.000
p21 0.320 0.3207 0.0233 0.0233 0.0005 0.960 1.000
p30 0.507 0.5044 0.0240 0.0250 0.0006 0.968 1.000
p31 0.391 0.3902 0.0241 0.0244 0.0006 0.962 1.000
term11 -0.116 -0.1148 0.0936 0.0981 0.0088 0.960 0.214
term10 0.354 0.3494 0.0944 0.0940 0.0089 0.952 0.956
term01 0.203 0.2028 0.0906 0.0934 0.0082 0.956 0.592
term00 0.640 0.6340 0.0850 0.0882 0.0072 0.960 1.000
de -0.287 -0.2846 0.0640 0.0627 0.0041 0.928 0.992
tie -0.470 -0.4642 0.1114 0.1213 0.0124 0.958 0.974
total -0.757 -0.7488 0.1196 0.1319 0.0143 0.980 1.000
pie -0.438 -0.4312 0.1040 0.1131 0.0108 0.966 0.972

103
Table 18: Hypothetical pollution data with a nominal mediator and a binary
outcome

X M Y Total
0 1 %
1 30 30 50 60
Ctrl 2 20 60 75 80
3 20 80 70 100
1 50 30 38 80
Tx 2 40 60 60 100
3 20 40 68 60

104
Table 19: Output for hypothetical pollution data with a nominal mediator and a
binary outcome, part 1

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-value

Latent class 1
y ON
x -0.511 0.346 -1.475 0.140
Thresholds
y$1 0.000 0.258 0.000 1.000
Latent class 2
y ON
x -0.693 0.329 -2.106 0.035
Thresholds
y$1 -1.099 0.258 -4.255 0.000
Latent class 3
y ON
x -0.693 0.371 -1.869 0.062
Thresholds
y$1 -1.386 0.250 -5.545 0.000

105
Table 20: Output for hypothetical pollution data with a nominal mediator and a
binary outcome, part 2

Two-Tailed
Parameter Estimates S.E. Est./S.E. P-value

Categorical latent variables


c#1 ON
x 0.799 0.236 3.379 0.001
c#2 ON
x 0.734 0.222 3.310 0.001
Intercepts
c#1 -0.511 0.163 -3.128 0.002
c#2 -0.223 0.150 -1.488 0.137
New/additional parameters
denom0 2.400 0.183 13.093 0.000
denom1 4.000 0.447 8.944 0.000
p10 0.250 0.028 8.944 0.000
p11 0.333 0.030 10.954 0.000
p20 0.333 0.030 10.954 0.000
p21 0.417 0.032 13.093 0.000
p30 0.417 0.032 13.093 0.029
p31 0.250 0.028 8.944 0.000
term11 0.542 0.032 16.842 0.000
term10 0.572 0.034 16.855 0.000
term01 0.679 0.032 21.077 0.000
term00 0.708 0.029 24.142 0.000
de -0.137 0.043 -3.145 0.002
tie -0.030 0.016 -1.860 0.063
total -0.167 0.044 -3.828 0.000
pie -0.029 0.015 -1.965 0.049
orde 0.549 0.106 5.199 0.000
ortie 0.886 0.058 15.306 0.000
orpie 0.872 0.060 14.517 0.000

106
Table 21: Output for mediation modeling with a count outcome, Step 2

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

y ON
x 0.300 0.3042 0.1743 0.1691 0.0303 0.936 0.432
m 0.400 0.4051 0.1042 0.1036 0.0109 0.946 0.964
xm 0.200 0.2004 0.1258 0.1251 0.0158 0.952 0.394
m ON
x 0.500 0.5016 0.0852 0.0863 0.0072 0.954 1.000
Intercepts
m 0.500 0.4999 0.0612 0.0611 0.0037 0.948 1.000
u -0.700 -0.7123 0.1226 0.1213 0.0152 0.956 1.000
Residual variances
m 0.750 0.7431 0.0490 0.0525 0.0024 0.960 1.000
New/additional parameters
ind 0.450 0.3036 0.0608 0.0632 0.0251 0.374 1.000
dir 0.400 0.4047 0.1323 0.1308 0.0175 0.942 0.860
ey1 0.670 0.6693 0.0759 0.0783 0.0057 0.952 1.000
ey0 0.497 0.4942 0.0600 0.0595 0.0036 0.956 1.000
mum1 1.000 1.0015 0.0639 0.0609 0.0041 0.936 1.000
mum0 0.500 0.4999 0.0612 0.0611 0.0037 0.948 1.000
ay1 0.900 0.8955 0.1111 0.1216 0.0123 0.960 1.000
ay0 0.600 0.6011 0.1571 0.1597 0.0246 0.956 0.958
bym11 1.450 1.4509 0.0628 0.0671 0.0039 0.962 1.000
bym10 1.900 1.9130 0.1582 0.1695 0.0251 0.964 1.000
bym01 1.300 1.3012 0.0807 0.0823 0.0065 0.956 1.000
bym00 1.600 1.6113 0.1834 0.1810 0.0337 0.950 1.000
eym11 2.086 2.1154 0.2193 0.2299 0.0489 0.956 1.000
eym10 1.545 1.5575 0.1154 0.1199 0.0134 0.960 1.000
eym01 1.584 1.6165 0.2251 0.2244 0.0516 0.952 1.000
eym00 1.297 1.3108 0.1120 0.1148 0.0127 0.946 1.000
tie 0.336 0.3668 0.0756 0.0773 0.0066 0.956 1.000
de 0.392 0.3930 0.0945 0.0948 0.0089 0.944 0.988
total 0.754 0.7598 0.1166 0.1156 0.0136 0.952 1.000
pie 0.143 0.1462 0.0508 0.0505 0.0026 0.942 0.942

107
Table 22: Output for Monte Carlo simulation, analyzing by M and Y regressed
on X only

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

y ON
x 0.000 0.6545 0.0877 0.0866 0.4360 0.000 1.000
m ON
x 0.500 0.4995 0.1033 0.0998 0.0107 0.952 1.000
y WITH
m 0.500 0.4978 0.0512 0.0498 0.0026 0.942 1.000
Intercepts
y 0.000 2.0014 0.0637 0.0611 4.0098 0.000 1.000
m 2.000 2.0000 0.0751 0.0705 0.0056 0.942 1.000
Residual variances
y 0.750 0.7486 0.0515 0.0529 0.0027 0.952 1.000
m 1.000 0.9956 0.0714 0.0704 0.0051 0.952 1.000
New/additional parameters
rhocurl 0.577 0.5760 0.0345 0.0334 0.0012 0.938 1.000
beta1 0.500 0.5000 0.0366 0.0354 0.0013 0.928 1.000
beta2 0.400 0.4049 0.0730 0.0729 0.0053 0.938 1.000
beta0 1.000 1.0014 0.0897 0.0867 0.0080 0.940 1.000
sig1 0.500 0.4984 0.0338 0.0352 0.0011 0.950 1.000
ind 0.250 0.2495 0.0543 0.0531 0.0029 0.952 1.000
de 0.400 0.4049 0.0730 0.0729 0.0053 0.938 1.000

108
Table 23: Output for generating data with true residual correlation 0.25 and
analyzing data with Imai’s ρ fixed at the true value 0.25

Estimates S.E. M.S.E. 95% % Sig

Parameter Population Average Std. Dev. Average Cover Coeff

y ON
x 0.000 0.6551 0.0975 0.0962 0.4386 0.000 1.000
m ON
x 0.500 0.5007 0.1033 0.0998 0.0107 0.956 1.000
y WITH
m 0.854 0.6743 0.0597 0.0586 0.0357 0.170 1.000
Intercepts
y 0.000 2.0016 0.0708 0.0679 4.0112 0.000 1.000
m 2.000 2.0003 0.0752 0.0705 0.0056 0.938 1.000
Residual variances
y 1.104 0.9251 0.0637 0.0654 0.0359 0.232 1.000
m 1.000 0.9957 0.0714 0.0704 0.0051 0.958 1.000
New/additional parameters
rho 0.250 0.2500 0.0000 0.0000 0.0000 0.000 1.000
rhocurl 0.812 0.7021 0.0262 0.0253 0.0129 0.002 1.000
beta1 0.500 0.5001 0.0366 0.0354 0.0013 0.928 1.000
beta2 0.400 0.4049 0.0732 0.0729 0.0054 0.938 1.000
beta0 1.000 1.0011 0.0892 0.0867 0.0079 0.944 1.000
sig1 0.707 0.3528 0.0121 0.0125 0.1257 0.000 1.000
ind 0.250 0.2502 0.0544 0.0532 0.0030 0.952 1.000
de 0.400 0.4049 0.0732 0.0729 0.0054 0.938 1.000

109
Table 24: Output for head circumference analysis using the Imai et al. sensitivity
approach with ρ = 0

Two-Tailed
Parameter Estimate S.E. Est./S.E. P-value

hcirc36 ON
alccig -0.079 0.115 -0.684 0.494
gender 0.697 0.082 8.467 0.000
eth 0.090 0.083 1.093 0.274
hcirc0 ON
alccig -0.366 0.108 -3.384 0.001
gender 0.345 0.079 4.363 0.000
eth 0.368 0.079 4.641 0.000
hcirc36 WITH
hcirc0 0.408 0.044 9.304 0.000
Intercepts
hcirc0 -0.301 0.071 -4.264 0.000
hcirc36 -0.400 0.073 -5.477 0.000
Residual variances
hcirc0 0.919 0.054 17.108 0.000
hcirc36 0.878 0.056 15.797 0.000
New/additional parameters
rho 0.000 0.000 0.000 1.000
rhocurl 0.454 0.036 12.566 0.000
beta1 0.444 0.040 11.074 0.000
beta2 0.084 0.106 0.790 0.429
beta0 -0.266 0.067 -3.983 0.000
sig1 0.000 0.000 0.000 1.000
indirect -0.162 0.050 -3.239 0.001
direct 0.084 0.106 0.790 0.429

110

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